Retroperitoneal angiomatoid fibrous histiocytoma: two cases of rare adult disease and a literature review

doi:10.21203/rs.3.rs-4820624/v1

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Case Report

Retroperitoneal angiomatoid fibrous histiocytoma: two cases of rare adult disease and a literature review

https://doi.org/10.21203/rs.3.rs-4820624/v1

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Background

Angiomatoid fibrous histiocytoma (AFH) is a rare and potentially low-grade malignant soft tissue tumor, more commonly found in children and young adults. It typically arises in the deep dermis and subcutaneous tissues of the limbs, followed by the trunk and head/neck regions. Retroperitoneal AFH is exceedingly rare, with local recurrence and metastasis even rarer occurrences.

Case presentation

This report presents clinical, imaging, biopsy, and molecular detection results from two cases of adult retroperitoneal AFH. One case experienced recurrence and metastasis one year post-surgery. Additionally, this article integrates these cases with a literature review of published instances of retroperitoneal AFH.

Conclusions

Retroperitoneal AFH is uncommon; patients with incomplete tumor capsules and surrounding invasion are predisposed to postoperative recurrence and metastasis. A definitive diagnosis relies on pathology. By detailing these two cases of retroperitoneal AFH, we aim to enhance medical professionals' understanding of this disease.

Angiomatoid fibrous histiocytoma

Retroperitoneum

Soft tissue tumor

Tomography

Angiomatoid fibrous histiocytoma (AFH) is a very rare mesenchymal tumor of uncertain differentiation, and local recurrence and metastasis occur even more rarely[1–5]. Because individuals often show clinical manifestations similar to those of other diseases, they are often initially misdiagnosed. AFH usually involves the limbs, followed by the trunk, head and neck, in children and young people[2,5–7]. There are few reported cases of AFH primarily in the retroperitoneum; to our knowledge, only 4 such cases have been reported to date[8–11] (Table 1). Here, we described 2 patients with AFH located in the retroperitoneum, one of whom recurred and metastasis 1 year after surgery. The diagnosis was confirmed based on immunohistochemical examination. This study was approved by the Ethics Committee of our Medical University

Table 1

Clinical data of patients with retroperitoneal angiomatoid fibrous histiocytoma
Study (year)	Patient gender	Patient Age	Clinical signs and symptoms	position	Size/cm	Imaging findings	Treatment	Molecular genetics	Prognosis
Case 1	Male	18-year-old	Abdominal pain and vomiting	Adrenal gland	5.7×5.1×4.5	CT: Shadow of cystic solid mass, boundary clearance,Significant enhancement of the solid part	Surgical resection	EWSR1 gene rearrangement	No recurrence after surgery
Case 2	Female	50-year-old	Abdominal pain	Adrenal gland	8×6.5×6	CT: Shadow of cystic solid mass, irregular, significant enhancement of the solid, part unclear local boundary with lymph node enlargement	Surgical resection	EWSR1 gene rearrangement	Recurrence and metastasis occurred one year after surgery
Gang Chen et al (2011)	Female	49-year-old	Abdominal pain and systemic inflammatory symptoms.	Between right adrenal gland and liver	5	/	Surgical resection	FUS rearranged	No recurrence in 9 months after surgery
LILI XIANG et al (2013)	Male	25-year-old	Fever and cough, moderate anemia	Left adrenal area	8×5×5	Fluorodeoxyglucose (FDG) metabolism was abnormally increased	/	/	No recurrence after surgery
Jonathan C et al (2018)	Male	9-year-old	Pain in the left side of spine/pelvis	Left psoas major muscle	12.7×5	MRI:A large multilobulated mass within the left psoas muscle	Puncture and drainage (recurrent bleeding) /Surgical resection	EWSR1 gene rearrangement	Postoperative recovered well
York Tien Lee et al (2019)	Female	11-year-old	/	/	/	/	/	/	/
Note: "/" indicates that data is missing.

Patient 1

An 18-year-old male experienced recurrent abdominal pain and vomiting for 2 weeks. Before admission, the patient had no obvious conditions that would lead to middle or upper abdominal pain or persistent pain. He also presented with dizziness, nausea, and vomiting, the latter consisting of the patient’s stomach contents. The patient had no fever, hematemesis, constipation, diarrhea or other discomfort. On physical examination, his BP was 83/30 mmHg. Laboratory examinations revealed the following: white blood cell (WBC) count, 16.21 (4.00 ~ 10.00) × 10 ⁹/L; platelets (PLT), 414 (100 ~ 300) × 10 ⁹/L; and neutrophils(NEU), 0.802 (0.5 ~ 0.7). No abnormalities in the levels of tumor markers were detected. There was no previous surgical history. Abdominal enhanced computed tomography (CT) revealed a cystic-solid low-density lesion in the right adrenal area with a clear boundary and a size of approximately 5.7×5.1×4.5 cm. The solid part of the tumor showed notable enhancement, but the cystic part did not (Fig. 1). On the basis of the imaging results, the possibility of pheochromocytoma was considered. Surgery: Retroperitoneal mass resection was performed under general anesthesia. During surgery, an oval tumor with a diameter of approximately 5.2 cm was observed in the right adrenal gland. The surface of the tumor was yellow, and a necrotic cavity could be observed. The tumor had a complete capsule with a smooth surface. The boundary with the normal adrenal tissue was unclear, whereas the boundary with surrounding tissues was clear. Immunohistochemistry revealed the following results: tumor tissues: CK (Pan) (+), vimentin (+), EMA (+), CD99 (+), desmin (+), CD68 (scattered +), CgA (-), Syn (-), S-100 (-), inhibin-a (-), MelanA (weak+), STAT6 (-), ALK (focal+), SMA (partial+), CD31 (-), ERG (-), FLI-1 (+), CD34 (small foci +), HMB45 (-), CD117 (-), CD21 (-), CD35 (-), CD56 (foci+), GFAP (-), and Ki-67 (+, hotspot area 5%). The pathological diagnosis was an AFH of the right adrenal gland. The EWSR1 gene was positive for breaks (Fig. 2). The patient had no recurrence after surgery, and his quality of life was good.

Patient 2

In a 50-year-old female, color Doppler ultrasound of the urinary system due to abdominal pain 6 days prior revealed a solid mass in the right adrenal region. Laboratory examination revealed that her WBC count was 11.76 (4.00–10.00×10 ⁹/L), and the patient reported no other discomfort. She had a past history of gallstones and cholecystitis. She had no relevant family history. Abdominal enhanced CT revealed an irregular, cystic-solid lobulated mass in the right adrenal gland area; the solid part was substantially enhanced on the enhanced scan, but the cystic part did not show enhancement. The boundary between the lesion and the right diaphragm was unclear, the upper pole of the right kidney was compressed, the surrounding fat space was blurred, and swollen lymph nodes were observed. CT revealed malignant adrenal tumor invasion to the right diaphragm and surrounding lymph node metastasis (Fig. 3A-B). Surgery: Retroperitoneal mass resection was performed under general anesthesia. During the surgery, a tumor approximately 8× 6.5× 6 cm in size, yellow in color, and with an intact capsule was observed in the right retroperitoneum, connected to the upper pole of the right kidney, the retroperitoneal cavity, the vena cava, and the surrounding tissues. To remove adhesions from the surrounding tissues, an electrosurgical knife was used to separate the tumor along the surface of the tumor capsule, and the tumor along with the right adrenal gland was removed. Postoperative report revealed that the right adrenal gland tumor was cystic and contained a thrombus-like substance. The cyst wall contained no lining epithelium but contained plentiful cholesterol crystals and hemosiderin deposition, and focal fusiform cell proliferation was observed (Fig. 4A-B). The mitotic rate was low. Immunohistochemistry revealed the following: D20226287-3: inhibin (-); CgA (-); Syn (foci +); CD56 (-); s-100 (-); Ki-67 (+, 10%); CR (-) CK (-); CD34 (-); vimentin (+); HMB45 (-); SMA (-); CD99 (+); BCL-2 (-); desmin (+); and CD31 (-). The results of special staining were as follows: D20226287-1: Masson's trichrome staining (-); hemosiderin staining (+). The pathological diagnosis was adrenal hemangioma with large areas of hemorrhage and necrosis and cystic degeneration.

One year after surgery, the patient developed recurrent fevers without obvious symptoms. Her maximum temperature was 38.6 degrees Celsius, and she presented with chills but no cough, sputum, dizziness, headache, or limb fatigue. Postoperative recurrence and metastasis in the para-aortic lymph nodes and left iliac crest were observed (Fig. 3C-D). Puncture of the left iliac crest and right adrenal gland was performed, and the pathological results suggested right adrenal gland AFH. The EWSR1 gene test was positive for breaks. Additional genetic testing suggested that the tumor was microsatellite stable (MSS) and programmed death ligand 1 (PD-L1)-negative and that there were no notable positive mutations. Immunohistochemistry revealed the following spindle-shaped cells: CD99 (diffuse +), desmin (+), and CD68 (partial +)(Fig. 4C-D).

After English-language scientific manuscript databases were searched beginning in 2011—when the first report of retroperitoneal AFH in a single patient was reported by Gang Chen et al.—only four publications were retrieved, describing a total of 4 patients pathologically diagnosed with retroperitoneal AFH[8–11]. Among them, 2 were male, and 2 were female, with ages ranging from 11–49 years; all the patients presented with clinical manifestations of abdominal pain and systemic inflammation, and the sizes of the tumors ranged from 5–12 cm. All patients underwent local tumor resection, and the postoperative recovery was satisfactory (Table 1).

AFH that primarily occurs in the retroperitoneum is extremely rare. This paper reports 2 cases of retroperitoneal AFH, both of which occurred in the adrenal glands; one patient recurred 1 year after surgery with metastasis in the lymph nodes and ilium. AFH grows slowly and has unclear differentiation, and the interior may demonstrate cystic degeneration and necrosis, which may be associated with hemorrhage in a small number of patients. The clinical manifestations of AFH, primarily in the retroperitoneum, are nonspecific; symptoms generally appear late and if the tumor is very large. The short axes of the 2 lesions in this study and the 4 lesions reviewed in the literature measured greater than 5 cm, and the adrenal gland was frequently involved (Table 1). Patients may present with symptoms such as abdominal pain, nausea, vomiting and, occasionally, systemic inflammatory symptoms related to tumor cytokines, such as fever, night sweats, anemia, and weight loss. Routine blood tests and tumor marker levels may not be substantially abnormal[8–11].

CT imaging of retroperitoneal AFHs often reveals a low-density or mixed-density mass. Cystic degeneration, necrosis, and hemorrhage are common within the tumor, which has a clear boundary, a capsule, and a solid region that is substantially enhanced after enhancement, often leading to a misdiagnosis of a neurogenic tumor or hemangioma[12]. In this case, the tumor density of these 2 patients indicated a cystic‒solid mass; the solid part was heterogeneously and significantly enhanced. The initial preoperative CT diagnoses, indicating hemangioma and pheochromocytoma for patients 1 and 2, respectively, were incorrect. Magnetic resonance imaging (MRI) can be used to visualize the following pathological features of AFH: (1) a fibrous pseudocapsule, presenting with a low signal and significant enhancement on T1-weighted (T1WI) and T2-weighted imaging (T2WI); (2) plasma cells, lymphocyte infiltration and tumor cells, appearing as a slightly low signal on T1WI and a slightly high signal on T2WI, both with significant enhancement; and (3) bleeding, in which MRI shows different signal manifestations due to differences in bleeding time, as well as the liquid‒liquid level[12–15]. Martinez et al. suggested that lymphocyte and plasma cell infiltration generally occurs at the edge of the fibrous pseudocapsule, which may be incomplete or missing in the presence of inflammatory or tumor cell infiltration and can be used as a sign of AFH infiltration on MRI[13]. PET-CT can reveal lesions and their locations, which is helpful for characterizing the lesion. ¹⁸F-FDG uptake could suggest histopathological features. Hemorrhagic cystic spaces often manifest as areas of reduced FDG metabolism, whereas tumor cells and surrounding lymphocytes and plasma cells show high FDG metabolism, frequently resulting in a misdiagnosis of a malignant tumor[16,17]. In a retrospective analysis of AFH patients by Ulaner et al.—19 patients who received imaging examinations before treatment—lymph node metastasis was suspected in 7 patients but confirmed by postoperative pathology in only one patient[18]. Lymph nodes with benign AFHs can show malignant lymph node features on imaging and are difficult to differentiate from metastatic lymph nodes. This may be due to the stimulation of inflammatory factors around the tumor, which results in reactive swelling and increased metabolism in the surrounding lymph nodes. In this group of patients, the lesion of one patient had an unclear local boundary and was accompanied by compression and invasion of the surrounding adjacent tissues and lymph nodes. However, only an abdominal CT examination was performed before surgery, and inflammatory reactive hyperplasia or metastasis of the swollen lymph nodes could not be evaluated. To reduce the invasiveness of the surgical procedure for AFH patients, additional studies with more patients are needed to improve the evaluation and management strategies employed by clinicians for assessing the lymph nodes.

Because retroperitoneal AFH is rare and has atypical clinical and radiological findings, it is easily misdiagnosed. The diagnosis of AFH depends on pathomorphology, immunohistochemistry and molecular detection, especially for atypical AFH, for which molecular detection is very important[14,19]. The pathological manifestations of AFH include the following: (1) arrangement of fibroblasts and tissue cells in a nodular pattern, with lipids and hemosiderin within the cells; (2) hemorrhage and hemorrhagic cystic cavities within most tumors; (3) chronic inflammatory cell infiltration, mainly lymphocytes and plasma cells; and (4) pseudocapsules formed by the proliferation of fibrous tissue around the tumor[3,7]. Immunohistochemistry for AFH is nonspecific; tumors are usually positive for vimentin, desmin, CD68, CD99, and EMA but negative for SMA, CK, CD21, CD31, CD34, CD35, FIIIRAg, clusterin, HMB-45, and S-100 [4–6]. The immunohistochemistry results of the 2 patients in this study were essentially consistent with those reported in the literature. AFH is considered an ectopic tumor. Currently, AFH is associated with three specific translocation-related gene fusion events, namely, EWSR1-CREB1, EWSR1-ATF1 and FUS-ATF1, which are considered highly important for the diagnosis of AFH. Among them, EWSR1-CREB1 is the most common, followed by EWSR1-ATF1[3,5,20,21]. In this report, both patients were EWSR1 gene rearrangement. On the basis of the results of other auxiliary examinations, the 2 patients were ultimately diagnosed with primary retroperitoneal AFH.

AFH is mostly an indolent disease, with a local recurrence rate of approximately 15% and a distant metastasis rate of < 5%; the tumor metastasizes mainly to the lymph nodes but also to the lung, liver, and brain[1,5,6]. A search of the literature revealed an additional 4 cases of retroperitoneal AFH, for a total of 6 cases. One patient recurred 1 year after surgery, with metastasis to the lymph nodes and ilium. An incomplete capsule and surrounding invasion make the tumor prone to postoperative recurrence[3,6]. Most patients can recover after wide local resection only. However, for patients in whom the lesions are located in the retroperitoneum and are difficult to remove, the recurrence and metastasis rates are relatively high after surgery. Radiotherapy or chemotherapy can be used as adjuvant therapy, and patients should be closely followed up to ensure timely diagnosis and treatment[5].

In conclusion, AFH is a rare tumor of uncertain differentiation, and retroperitoneal AFH is even rarer. We further improved our understanding of this tumor by reporting two cases of retroperitoneal AFH (confirmed by biological analysis). Owing to nonspecific clinical symptoms and radiological manifestations, preoperative diagnosis is often difficult, and the final diagnosis depends on pathology. Wide local excision is the main treatment method. However, patients with incomplete tumor capsules and surrounding invasion are prone to recurrence and metastasis after surgery; thus, close clinical follow-up should be performed.

Ethics approval and consent to participate

Our study was approved by the second affiliated hospital ethics committee of Guangxi medical university. Approval Number: 2024-KY(0491). Informed consent was obtained from all the participants.

Availability of data and materials

Availability of data and materials: The datasets generated and analyzed in the present study are not publicly available due to privacy, but can be obtained from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

This work was supported by the Natural Science Foundation of Guangxi (contract grant number: 2023GXNSFBA026120); and Chongzuo Science and Technology Plan Project（contract grant number: 20220628）

Authors' contributions

ML: data collection, writing-original draft preparation. ZX and NL: data procession, writing—original draft preparation. XY and GX:software, validation. FZ: supervision, writing-reviewing, and editing. All authors reviewed the manuscript.

Acknowledgements

The authors thank for patients and their family for their interest and cooperation.

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No competing interests reported.

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You are reading this latest preprint version

Retroperitoneal angiomatoid fibrous histiocytoma: two cases of rare adult disease and a literature review

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Abstract

Background

Case presentation

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Introduction

Case presentation

Patient 1

Patient 2

Discussion

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